The Role of AMPK Signaling in Brown Adipose Tissue Activation

Obesity is becoming a pandemic, and its prevalence is still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as a possible target to achieve this for its functional role in energy expenditure by means of increasing thermogenesis. An important metabolic sensor and regulator of whole-body energy balance is AMP-activated protein kinase (AMPK), and its role in energy metabolism is evident. This review highlights the mechanisms of BAT activation and investigates how AMPK can be used as a target for BAT activation. We review compounds and other factors that are able to activate AMPK and further discuss the therapeutic use of AMPK in BAT activation. Extensive research shows that AMPK can be activated by a number of different kinases, such as LKB1, CaMKK, but also small molecules, hormones, and metabolic stresses. AMPK is able to activate BAT by inducing adipogenesis, maintaining mitochondrial homeostasis and inducing browning in white adipose tissue. We conclude that, despite encouraging results, many uncertainties should be clarified before AMPK can be posed as a target for anti-obesity treatment via BAT activation.

Download Full-text

Front cover: Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201770111 ◽

2017 ◽

Vol 61 (11) ◽

pp. 1770111

Author(s):

Yilin You ◽

Xiaoxue Yuan ◽

Xiaomeng Liu ◽

Chen Liang ◽

Minghui Meng ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Metabolism ◽

Brown Adipose Tissue ◽

Mitochondrial Function ◽

Whole Body ◽

Front Cover ◽

Brown Adipose ◽

Body Energy

Download Full-text

Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in α1-AMPK−/− mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00444.2010 ◽

2011 ◽

Vol 301 (2) ◽

pp. R473-R483 ◽

Cited By ~ 20

Author(s):

Jake D. Bauwens ◽

Eric G. Schmuck ◽

Christopher R. Lindholm ◽

Rebecca L. Ertel ◽

Jacob D. Mulligan ◽

...

Keyword(s):

Adipose Tissue ◽

Cold Exposure ◽

Whole Body ◽

Nonshivering Thermogenesis ◽

Wild Type ◽

Brown Adipose ◽

Ampk Activity ◽

Amp Activated Protein Kinase ◽

Established Role

Recent studies indicate that a substantial amount of metabolically active brown adipose tissue (BAT) exists in adult humans. Given the unique ability of BAT to convert calories to heat, there is intense interest in understanding the regulation of BAT metabolism in hopes that its manipulation might be an effective way of expending excess calories. Because of the established role of AMP-activated protein kinase (AMPK) as a “metabolic master switch” and its extremely high levels of activity in BAT, it was hypothesized that AMPK might play a central role in regulating BAT metabolism. To test this hypothesis, whole body α1-AMPK−/− (knockout) and wild-type mice were studied 1) under control (room temperature) conditions, 2) during chronic cold exposure (14 days at 4°C), and 3) during acute nonshivering thermogenesis (injection of a β3-adrenergic agonist). Under control conditions, loss of α1-AMPK resulted in downregulation of two important prothermogenic genes in BAT, thyrotropin-releasing hormone (−9.2-fold) and ciliary neurotrophic factor (−8.7-fold). Additionally, it caused significant upregulation of α2-AMPK activity in BAT, white adipose tissue, and liver, but not cardiac or skeletal muscle. During acute nonshivering thermogenesis and chronic cold exposure, body temperature was indistinguishable in the α1-AMPK−/− and wild-type mice. Similarly, the degree of cold-induced hyperphagia was identical in the two groups. We conclude that α1-AMPK does not play an obligatory role in these processes and that adaptations to chronic loss of α1-AMPK are able to compensate for its loss via several mechanisms.

Download Full-text

The functional role of brown adipose tissue in whole‐body lipid metabolism in humans (1160.3)

The FASEB Journal ◽

10.1096/fasebj.28.1_supplement.1160.3 ◽

2014 ◽

Vol 28 (S1) ◽

Author(s):

Maria Chondronikola ◽

Craig Porter ◽

Nicholas Hurren ◽

Tony Chao ◽

Christina Yfanti ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Brown Adipose Tissue ◽

Functional Role ◽

Whole Body ◽

Body Lipid ◽

Brown Adipose

Download Full-text

Brown Adipose Tissue - role in metabolic disorders

IMC Journal of Medical Science ◽

10.3329/imcjms.v13i1.42049 ◽

2019 ◽

Vol 13 (1) ◽

pp. 002

Author(s):

Tahniyah Haq ◽

Frank Joseph Ong ◽

Sarah Kanji

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Metabolic Diseases ◽

Uncoupling Protein ◽

Whole Body ◽

Positron Emission ◽

Brown Adipose ◽

Magnetic Resonance Imaging Mri ◽

Fdg Pet Ct ◽

Body Energy

Brown adipose tissue, a thermogenic organ, previously thought to be present in only small mammals and children has recently been identified in adult humans. Located primarily in the supraclavicular and cervical area, it produces heat by uncoupling oxidative phosphorylation due to the unique presence of uncoupling protein 1 by a process called nonshivering thermogenesis. BAT activity depends on many factors including age, sex, adiposity and outdoor temperature. Positron-emission tomography using 18F-fluorodeoxyglucose and computed tomography (18F-FDG PET–CT), magnetic resonance imaging (MRI) and thermal imaging (IRT) are among several methods used to detect BAT in humans. The importance of BAT is due to its role in whole body energy expenditure and fuel metabolism. Thus it is postulated that it may be useful in the treatment of metabolic diseases. However, there are still many unanswered questions to the clinical usefulness of this novel tissue. IMC J Med Sci 2019; 13(1): 002

Download Full-text

Leucine Potentiates Glucose-mediated 18F-FDG Uptake in Brown Adipose Tissue via β-Adrenergic Activation

Biomedicines ◽

10.3390/biomedicines8060159 ◽

2020 ◽

Vol 8 (6) ◽

pp. 159

Author(s):

Brenda Huska ◽

Sarah Niccoli ◽

Christopher P. Phenix ◽

Simon J. Lees

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Whole Body ◽

Fdg Uptake ◽

Standardized Uptake Values ◽

Positron Emission ◽

Brown Adipose ◽

18F Fdg ◽

Adrenergic Activation

Significant depots of brown adipose tissue (BAT) have been identified in many adult humans through positron emission tomography (PET), with the amount of BAT being inversely correlated with obesity. As dietary activation of BAT has implications for whole body glucose metabolism, leucine was used in the present study to determine its ability to promote BAT activation resulting in increased glucose uptake. In order to assess this, 2-deoxy-2-(fluorine-18)fluoro-d-glucose (18F-FDG) uptake was measured in C57BL/6 mice using microPET after treatment with leucine, glucose, or both in interscapular BAT (IBAT). Pretreatment with propranolol (PRP) was used to determine the role of β-adrenergic activation in glucose and leucine-mediated 18F-FDG uptake. Analysis of maximum standardized uptake values (SUVMAX) determined that glucose administration increased 18F-FDG uptake in IBAT by 25.3%. While leucine did not promote 18F-FDG uptake alone, it did potentiate glucose-mediated 18F-FDG uptake, increasing 18F-FDG uptake in IBAT by 22.5%, compared to glucose alone. Pretreatment with PRP prevented the increase in IBAT 18F-FDG uptake following the combination of glucose and leucine administration. These data suggest that leucine is effective in promoting BAT 18F-FDG uptake through β-adrenergic activation in combination with glucose.

Download Full-text

Brown adipose tissue transplantation improves whole-body energy metabolism

Cell Research ◽

10.1038/cr.2013.64 ◽

2013 ◽

Vol 23 (6) ◽

pp. 851-854 ◽

Cited By ~ 116

Author(s):

Xiaomeng Liu ◽

Zongji Zheng ◽

Xiaoming Zhu ◽

Minghui Meng ◽

Lan Li ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Metabolism ◽

Brown Adipose Tissue ◽

Tissue Transplantation ◽

Whole Body ◽

Brown Adipose ◽

Body Energy

Download Full-text

Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201700261 ◽

2017 ◽

Vol 61 (11) ◽

pp. 1700261 ◽

Cited By ~ 27

Author(s):

Yilin You ◽

Xiaoxue Yuan ◽

Xiaomeng Liu ◽

Chen Liang ◽

Minghui Meng ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Metabolism ◽

Brown Adipose Tissue ◽

Mitochondrial Function ◽

Whole Body ◽

Brown Adipose ◽

Body Energy

Download Full-text

Does Adipose Tissue Thermogenesis Play a Role in Metabolic Health?

Journal of Obesity ◽

10.1155/2013/204094 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4

Author(s):

Craig Porter ◽

Elisabet Børsheim ◽

Labros S. Sidossis

Keyword(s):

Adipose Tissue ◽

Energy Metabolism ◽

Brown Adipose Tissue ◽

Metabolic Diseases ◽

Oxidative Capacity ◽

Whole Body ◽

Research Strategies ◽

Brown Adipocytes ◽

Brown Adipose

The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation. Recently, brown adipose tissue depots have been identified in adult humans. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of ATP production, has led to renewed interest in the role that these adipocytes play in human energy metabolism. In our view, there is a need for robust physiological studies determining the relationship between molecular signatures of brown adipose tissue, adipose tissue mitochondrial function, and whole body energy metabolism, in order to elucidate the significance of thermogenic adipose tissue in humans. Until such information is available, the role of thermogenic adipose tissue in human metabolism and the potential that these adipocytes may prevent or treat obesity and metabolic diseases in humans will remain unknown. In this article, we summarize the recent literature pertaining to brown adipose tissue function with the aims of drawing the readers’ attention to the lack of data concerning the role of brown adipocytes in human physiology, and to the potential limitations of current research strategies.

Download Full-text

Allicin regulates energy homeostasis through brown adipose tissue

10.1101/713305 ◽

2019 ◽

Author(s):

Chuanhai Zhang ◽

Xiaoyun He ◽

Yao Sheng ◽

Jia Xu ◽

Cui Yang ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Energy Homeostasis ◽

Metabolic Diseases ◽

Whole Body ◽

Brown Adipocyte ◽

Brown Adipose ◽

Promising Therapeutic Approach ◽

Treatment Of Obesity

AbstractBackground/objectives:Disorder of energy homeostasis can lead to a variety of metabolic diseases, especially obesity. Brown adipose tissue (BAT) is a promising potential therapeutic target for the treatment of obesity and related metabolic diseases. Allicin, a main bioactive ingredient in garlic, has multiple biology and pharmacological function. However, the role of Allicin, in the regulation of metabolic organ, especially the role of activation of BAT, has not been well studied. Here, we analyzed the role of Allicin in whole-body metabolism and the activation of BAT.Results:Allicin had a significant effect in inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, improving insulin resistance, and ameliorating hepatic steatosis in diet-introduced obesity (DIO) mice. Then we find that Allicin can strongly activate brown adipose tissue (BAT). The activation of brown adipocyte treated with Allicin was also confirmed in mouse primary brown adipocytes.Conclusion:Allicin can ameliorate obesity through activating brown adipose tissue. Our findings provide a promising therapeutic approach for the treatment of obesity and metabolic disorders.

Download Full-text